Homoplasmic deleterious MT-ATP6/8 mutations in adult patients

To assess the frequency of complex V defects, a team of French researchers including researchers from the Institute of Myology systematically sequenced the MT-ATP6 / 8 genes in 512 consecutive patients. They performed functional analysis in muscle or fibroblasts for 12 of the 27 putative homoplasmic mutations and in cybrids for 4 of them. Fibroblasts, muscles and cybrids with known deleterious mutations were tested in parallel: spectrophotometric tests for oxidative phosphorylation, western blots, structural analysis, ATP production, glycolysis and evaluation of cell proliferation.

The researchers demonstrated the deleterious nature of three original mutations. A striking gradation in the severity of the consequences of mutations and differences between muscle, fibroblasts and cybrids implied a likely underdiagnosis of human V complex defects.


Homoplasmic deleterious MT-ATP6/8 mutations in adult patients. Rucheton B, Jardel C, Filaut S, Del Mar Amador M, Maisonobe T, Serre I, Beatriz Romero N, Leonard-Louis S, Haraux F, Lombès A. Mitochondrion. 2020 Aug 25. pii: S1567-7249(20)30173-2. doi: 10.1016/j.mito.2020.08.004. [Epub ahead of print]